miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease

Abstract

BackgroundCirculating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.ObjectivesThe aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.MethodsLevels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR).ResultsThe median follow-up period was 4 years (IQR 2.78–5.04). The median age of all patients was 64 years (IQR 57–69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89).ConclusionSerum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.

microRNAs in cardiovascular disease – clinical application

“…The group identified miR-126, miR-197, and miR-223 to reliably predict future MI in 820 individuals from the Bruneck study [97] (for further details on the Bruneck study, see [31]). These results were recently validated [98] by identifiying miR-197 and miR-223, as well as miR-126, as strong predictors of cardiovascular death in a large cohort of 873 patients with invasively diagnosed CAD [98]. These results not only transfer the diagnostic potential of miRNAs in CVD to a prognostic level, they also indicate the promising applicability of miRNAs as useful biomarkers in primary and secondary prevention in CVD.…”

Diagnostic and prognostic value of biomarkers in acute myocardial infarction

“…Oerlemans et al 74 revealed that the combination of miR-1, miR-21 and miR-499 had a higher diagnostic value than hs-troponin T. In addition to diagnostic value, miRNAs may be more useful for risk stratification and can be used as prognostic biomarkers 75. Circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with coronary artery disease 76. Studies also found that miRNA-134, miRNA-328, miRNA-34a and miRNA-208b were associated with the development of heart failure and increased risk of mortality after AMI 77 78…”

The role of miRNAs in cardiovascular disease risk factors

“…Additional studies revealed that miR-223 directly targets SR-B1, HMGCS1, and methylsterol monooxygenase 1(SC4MOL) for modulation of HDL-C uptake and cholesterol biosynthesis 102 . The finding that miR-223 is elevated in CAD patient’s serum 103 adds a layer of complexity to the role of miR-223 in the pathogenesis of CAD. One explanation is that miR-223 has pleiotropic physiologic roles thus, its upregulation in serum may serve as a biomarker of disease or compensatory mechanism rather than a direct modulator of the pathophysiology of disease.…”